Important results of laboratory

2024

1. A series of new environmentally safe mono- and dicarbamate-containing piperidinium surfactants has been obtained for the creation of pesticide nanocompositions. The introduction of carbamate fragments reduces the aggregation threshold, toxicity, provides surfactant biodegradability, and polyfunctional activity (high solubilization, membrane-tropic, antimicrobial properties, catalytic effect in reactions of organophosphorus pesticide decomposition). Based on surfactants and the insecticide imidacloprid, nanocompositions have been formed that allow, in low dosages (0.1% by weight), to increase the effectiveness of imidacloprid against the insect pest greenhouse whitefly (Trialeurodes vaporariorum) by an order of magnitude.

2023

1. For the first time, cationic liposomes modified with new carbamate-containing gemini surfactants were obtained and their composition was optimized for multitarget delivery of α-tocopherol (antioxidant) and donepezil hydrochloride (acetylcholinesterase inhibitor) to the brain of transgenic mice with a model of Alzheimer's disease. In vivo tests showed that intranasal administration of liposomal compositions for 21 days leads to an improvement in both cognitive functions in transgenic animals and a decrease in the level of amyloid deposits in the hippocampus and entorhinal cortex of the brain.
2. New non-toxic drug delivery systems based on supra-amphiphiles formed in mixed compositions of amphiphilic calix[4]resorcinol substituted at the upper rim with viologen groups with various biopolymers (sodium salts of RNA, alginic acid, carboxymethylcellulose, and casein) have been obtained. Due to the cooperative contribution of hydrophobic and electrostatic interactions between oppositely charged components, spontaneous formation of pH-sensitive nanoparticles is realized in an aqueous medium under mild conditions. The obtained nanoparticles are capable of encapsulating drugs of various nature, providing their selective cytotoxicity toward tumor cell line M-HeLa.

2022

1. Nanosized carriers (liposomes, transfersomes, microemulsions, nanoemulsions, emulgels) have been developed for transdermal therapy of inflammatory processes and poisoning with toxic organophosphates. In vitro, ex vivo and in vivo testing has shown that modification of nanocontainers with cationic amphiphiles and optimization of the composition leads to a significant improvement in anti-inflammatory and wound-healing activity, significantly exceeding the effectiveness of commercial drugs. For the first time, a gel form of the acetylcholinesterase reactivator pralidoxime chloride has been developed, capable of increasing the survival of rats from 55% to 90% in the case of prophylactic transdermal therapy.
2. New multifunctional compositions based on cationic surfactants and hydrotropes (amino acids, sodium salicylate, sodium adenosine triphosphate, urea, choline, ethanolamines, and polyelectrolytes of various nature) have been created, capable of repeatedly increasing the solubility of hydrophobic substrates. The factors (structure, charge and concentration of components, presence of ionogenic groups, pH) controlling the mechanism of hydrotropic effect on the aggregation threshold of surfactants, morphology, solubilization activity have been established. Based on the identified patterns, micellar nanocontainers for hydrophobic medicinal substances with adjustable parameters and high loading efficiency have been developed. The obtained data expand the understanding of the mechanism of action of hydrotropes and the field of biomedical application of surfactants.

2021

1. New micellar compositions based on hydroxypiperidinium surfactants have been obtained that have multifunctional activity as (1) biomimetic nanoreactors of selective action for the concentration and decomposition of toxic organophosphorus compounds, carboxylic acid esters and polyaromatic pollutants; (2) antimicrobial agents active both against pathogenic strains of animals and plants; (3) adjuvants that increase the efficiency of surface wetting and increase the transport of agrochemicals into the plant. A wide range of practical properties is due to the high solubilizing ability of hydroxypiperidinium surfactants and membranotropic properties.
2. New mitochondria-targeted nanocontainers of two types have been obtained: liposomal formulations and nanocomposite systems based on mesoporous silica nanoparticles non-covalently modified with cationic surfactants. It was shown for the first time that not only triphenylphosphonium, but also imidazolium cations are capable of imparting targeting properties to cell mitochondria. According to confocal microscopy data, modification of liposomal systems makes it possible to increase their accumulation in mitochondria up to 30%.

2020

1. For the first time, a successful in vivo application of cationic liposomes non-covalently modified with synthetic gemini surfactants for the reactivation of cerebral acetylcholinesterase after poisoning with organophosphorus compounds by intravenous administration of the antidote pralidoxime chloride (2-PAM) was carried out. The developed liposomal form made it possible to eliminate the established intravenous limitations associated with high toxicity and hemagglutination caused by cationic liposomes, and to achieve 27% reactivation of brain acetylcholinesterase.

2019

1. With the aim of targeted delivery of drugs into mitochondria, new stable cationic liposomes were obtained by non-covalent inclusion of imidazolium and triphenylphosphonium surfactants into the lipid bilayer. A higher degree of colocalization of cationic liposomes with mitochondria in comparison with unmodified analogs was proved by confocal microscopy. The modified liposomes exhibit stability for several months, improved encapsulation efficiency, prolonged release of drug compounds, and high cytotoxicity against PANC-1 pancreatic carcinoma cells.